The present invention relates to magnetic particles, a method for producing the same, and probe-bonded particles.
Since magnetic particles can be easily applied to washing of materials by magnetic separation and can provide an outstanding reaction field in the researches of antigen-antibody immunoreactions, hybridization of DNAs or DNA and RNA, interactions of pharmaceutical candidate substances and in vivo substances, and the like, the magnetic particles are being actively used in the biochemical field, particularly in the research of diagnostic agents and pharmaceuticals in recent years.
Particularly as biochemical carrier particles, polystyrene particles are mainly used for physical adsorption sensitization, and polystyrene particles modified with a carboxyl group are mainly used for chemical bond sensitization. However, these particles adsorb a large amount of physiologically active substances existing in test samples such as cells, proteins, and DNAs which are not the target substances. Such adsorption of non-target substances is herein referred to as “non-specific adsorption”. The non-specific adsorption hinders performance of sensitization particles. That is, the non-specific adsorption has been a serious hindrance when using these particles.
As a biochemical carrier exhibiting only small non-specific adsorption, gels based on sugar chains such as agarose and sepharose are used. These gels, however, tend to reduce the activity of bonded probes and cannot emit a sufficient number of signals in many cases.
Reducing non-specific adsorption is also demanded for magnetic particles. To this end, magnetic particles with glycidyl groups introduced onto the particle surface have been proposed. For example, JP-A-2006-131771 proposes a method of dispersing superparamagnetic particles in styrene and glycidyl methacrylate and polymerizing while finely dispersing the mixture by supersonic treatment. However, not only this method cannot sufficiently cover magnetic materials with glycidyl methacrylate to adequately reduce the non-specific adsorption, but also the average diameter of the resulting particles is 200 nm or less, which is too small for the particles to exhibit sufficient magnetic separation performance.
The applicant of this invention has disclosed a method for manufacturing magnetic particles comprising a step of providing a two layer polymer coat in order to efficiently produce particles for diagnostic agents having a uniform diameter and being free from release of magnetic materials or elution of substances originating from magnetic material components such as iron ion (Japanese Patent No. 3738847). The applicant further disclosed magnetic particles with reduced non-specific adsorption (JP-A-2005-83904 and JP-A-2005-83905). However, further reduction of non-specific adsorption is desired.
Although the objective is not necessarily reducing the non-specific adsorption, JP-T-2-501753, for example, discloses a method for producing magnetic particles with glycidyl groups introduced therein by polymerizing a mixture of a magnetic material and a monomer in the presence of nuclear particles, and coating the resulting polymer. However, since only a very small amount of the mixture of the magnetic material and the monomer polymerize on the nuclear particles, only a very small amount of magnetic materials can be incorporated into the nuclear particles. The product thus exhibits poor magnetic separation properties.
JP-T-10-505118 discloses a reaction for introducing amino groups into magnetic particles with glycidyl groups introduced therein. The resulting magnetic particles are porous particles to be used for an ion-exchange purposes having remarkable non-specific adsorption.
JP-T-2006-511935 proposes a method of causing a magnetic material to deposit on the surface and inside of particles and coating the particles with a polymer having glycidyl groups. However, according to this method, when magnetic particles are caused to deposit on the particle surface, the polymer having glycidyl groups can be coated only insufficiently, failing to reduce the non-specific adsorption.